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A Lasson

Publications and source records attributed to A Lasson.

At least 73 records · Page 4Linked to original sources
PubMed1984

On the potential role of trypsin and trypsin inhibitors in acute pancreatitis.

The protective role of alpha 2-macroglobulin, alpha 1-antitrypsin and Aprotinin against trypsin-induced effects on C3 and kininogen was studied in a human in vitro model. When human cationic trypsin was added to human serum or plasma, there was a gradual saturation of alpha 2-macroglobulin and later of alpha 1-antitrypsin. When alpha 2-macroglobulin was 70% saturated, there was a prompt cleavage of both C3 and kininogen, in spite of 80% free and active alpha 1-antitrypsin. These biochemical changes and antiprotease levels are identical to our findings in patients with acute pancreatitis, especially in their peritoneal exudate. Very high concentrations of Aprotinin, 5-15 times higher than ever used clinically, blocked the cleavage of both C3 and kininogen, while doses commonly used clinically were without significant effect. The clinical implications are: A trypsin-induced activation of both the complement and kinin system with clinical consequence is possible in patients with acute pancreatitis because of very low alpha 2-macroglobulin levels. Aprotinin in adequate doses, 5-15 times higher than ever used clinically, seems to protect against activation of two systems.

Acute Disease↗
PubMed1984

Gabexate mesilate (FOY) and aprotinin. A comparative study of the effects on trypsin-induced activation of the kinin and complement systems in vivo and in vitro.

The effect of gabexate mesilate (FOY) was studied in vitro in human and canine serum upon the addition of trypsin, and in vivo in dogs during intravenous trypsin infusion. The effect of FOY was compared with the effect of aprotinin. FOY did not show any protection against trypsin-induced activation of the complement and kinin systems in vitro or in vivo, while aprotinin did. All dogs exhibited signs of circulatory shock together with a consumption of the two main proteinase inhibitors, alpha-macroglobulin and alpha 1-proteinase inhibitor, when intravenous infusions of FOY and trypsin were performed simultaneously. However, all dogs survived without signs of shock if aprotinin was given instead of FOY. The ineffectiveness of FOY in serum is explained by the complete dissociation of FOY trypsin complexes together with a rapid degradation of FOY to inactive metabolites. Although FOY is an effective proteinase inhibitor in defined buffer systems in vitro, the results of the present study indicate that it is not an effective proteinase inhibitor in vivo. Aprotinin protects against trypsin-induced activation reactions, although much higher concentrations are needed in human than in canine serum.

Animals↗
PubMed1984

Aprotinin turn-over studies in dog and in man with severe acute pancreatitis.

The elimination of aprotinin after intravenous infusion was exponential until 95% of the dose was cleared from the plasma after 1 h in dogs with bile-induced pancreatitis. The half-life of this part of the elimination was 10 min. The concentration of aprotinin in the peritoneal fluid reached a maximum plateau after 1 h. Direct intra-abdominal infusion of aprotinin was followed by a relatively slow elimination of the inhibitor from the cavity. One hour after the infusion the concentration of aprotinin in the peritoneal exudate was about 50% of the initial value. Four hours later the concentration of inhibitor with unchanged immunoreactivity and inhibiting capacity was still about 25% of the initial value. Based on the results of this experimental study an intraperitoneal dosage schedule for aprotinin was tested in three patients with haemorrhagic pancreatitis. A total amount of 14 X 10(6) KIU was given in repeated dosages during 18 h. This resulted in a minimum level of aprotinin in the peritoneal exudate of about 10 mumol/l. According to our earlier published data this level should largely block trypsin-induced effects relevant in pancreatitis. In conclusion; due to the rapid elimination of aprotinin from plasma, after i.v. application a therapeutically useful concentration is never reached in the peritoneum, while the elimination from the peritoneum is relatively slow, thus providing therapeutically useful concentrations which can be maintained for some time after i.p. application.

Acute Disease↗
PubMed1984

Protease inhibitors in acute human pancreatitis. Correlation between biochemical changes and clinical course.

A clinical and biochemical analysis of 27 attacks of acute pancreatitis was made throughout the course of the disease. In severe attacks alpha 2-macroglobulin (alpha 2-M) decreased during the first days, reaching values in blood below 40% of the normal value. In addition, this remaining alpha 2-M had a decreased trypsin-binding capacity, indicating circulating alpha 2-M protease complexes. The inter-alpha-trypsin inhibitor concentration was also decreased, whereas alpha 1-proteinase inhibitor, antichymotrypsin, and pancreatic secretory trypsin inhibitor increased. All changes were most pronounced in the peritoneal fluid and were also closely correlated to the severity of the disease, assessed by both Ranson's and McMahon's classification systems. All patients with clinical complications had profound biochemical changes. In accordance with earlier findings, activation of both the complement and kinin systems seems possible in both blood and peritoneal fluid at the low alpha 2-M concentrations found in severe attacks.

Acute Disease↗
PubMed1984

Trypsin-alpha 1-protease inhibitor complexes in serum and clinical course of acute pancreatitis.

The levels of amylase, trypsinogen, and trypsin-alpha 1-protease inhibitor complexes, both in serum and in peritoneal fluid, were correlated to the severity and clinical course in 27 attacks of acute pancreatitis. Serum levels of trypsin-alpha 1-protease inhibitor complexes on admission correlated well with the severity and clinical course of the disease, whereas serum levels of amylase and trypsinogen did not. This may be of clinical importance in differentiating severe acute pancreatitis from milder and self-limiting forms of the disease.

Acute Disease↗
PubMed1984

Acute pancreatitis in man. A clinical and biochemical study of pathophysiology and treatment.

The correlation between clinical course, protease inhibitors, complement and kinin activation was studied in vivo in 27 attacks of acute pancreatitis and also in vitro. The value of peritoneal lavage was retrospectively analyzed in 73 pancreatitis attacks. The effect of aprotinin was studied in vitro. Complement and kinin activation occurred in vitro when alpha-macroglobulin (alpha 2-M) concentration was below 35%, in spite of 90% free and reactive alpha 1-protease inhibitor. These low alpha 2-M levels were found in the general circulation in severe attacks. Functional alpha 2-M levels were lower than electroimmunoassay values during the acute disease. Complement and kinin activation was present both in blood and in peritoneal fluid. The extent of activation was closely correlated to the severity of the pancreatitis attack. Classical as well as alternative complement activation occurred. Kinin activation was caused by plasma kallikrein as well as by other kininogenases. Functional kallikrein inhibition was lower than electroimmunoassay values for the C1 inactivator. High levels of activated trypsin was found in complex with alpha 1-protease inhibitor in severe attacks. These findings together with the low functional alpha 2-M and a possible functional deficiency also of the C1 inactivator make trypsin-induced activation of the complement as well as the kinin system possible in acute pancreatitis. Changes in proteases and protease inhibitors were most pronounced in the peritoneal fluid, functional alpha 2-M and C1 inactivator being zero, indicating that the primary event occurs locally in and around the pancreas. Peritoneal lavage thus ought to be beneficial. The good results achieved with peritoneal lavage in the retrospective analysis of the 73 clinically severe attacks seem to verify this conclusion. The biochemical changes seen in vivo indicate alpha 2-M and C1 inactivator to be most important against proteolytic activation of the complement and kinin systems. Treatment with purified protease inhibitors might be beneficial. This also seems to be true of aprotinin, according to the in vitro results, provided very high doses are used. All antiprotease therapy seems to be most important intraperitoneally.

Acute Disease↗
PubMed1984

Peritoneal lavage in severe acute pancreatitis.

An analysis is presented of 73 attacks of acute pancreatitis treated with non-operative peritoneal lavage, classified according to Ranson's 11 signs and followed up for on average four years. None of the 21 moderate attacks was associated with complications or mortality. In the 52 severe attacks, four patients (7.7%) died, new pseudocyst developed in five patients (9.6%) and abscess in four (7.7%), and diabetes was found in 12 patients (23%) at follow-up. In all these respects the severe attacks showed statistically significant difference from the moderate attacks, as did the need for assisted ventilation, the volume of gastric retention and the length of hospital stay. The authors conclude that non-operative peritoneal lavage is beneficial, probably by removing toxic substances from the peritoneal cavity.

Acute Disease↗
PubMed1983

Endocrine tumors of the duodenum. Clinical characteristics and hormone content.

Nineteen patients with primary duodenal carcinoid were analysed retrospectively, and eight of the tumors were immunocytochemically examined. One tumor contained somatostatin, two tumors gastrin, two tumors both these peptides, and one tumor contained serotonin. In two tumors no peptide or amine could be demonstrated. Eight patients had ulcer symptoms and nine had gallstone disease. Only four patients had metastatic spread in spite of long delay. Five-year survival was 75% in 12 operated patients. No patient died of the tumor per se. It is concluded that a simple excision seems justified when the tumor is smaller than 2 cm, while probably more extensive surgery is needed when the tumor is larger or when there is local spread. Modern techniques of histofluorescence and immunocytochemistry facilitating a more precise classification will probably result in a better understanding as to symptomatology, prognosis, and making possible better treatment in the heterogenous group of carcinoid tumors.

Adult↗
PubMed1983

Influence of plasma proteinase inhibitors and aprotinin on trypsin-induced bradykinin release in vitro in man.

The consumption of kininogen (measured as kinin-releasable material) was studied in an experimental model in vitro. Analyses were made following the addition of increasing amounts of human cationic trypsin to human serum and plasma. The consumption of kininogen was correlated with the degree of saturation of the plasma proteinase inhibitors alpha 2-macroglobulin (alpha 2-M) and alpha 1-proteinase inhibitor (alpha 1-PI) with trypsin in the presence and absence of aprotinin (Trasylol). The level of kininogen fell dramatically when alpha 2-M was saturated to 70% in spite of 90% free alpha 1-PI. Trypsin-alpha 2-M complexes had no effect on kininogen levels. 60 mumol/l of aprotinin, i.e. approximately 3 X 10(6) KIU/l, blocked only 60% of the trypsin-induced kininogen consumption in serum, while 15 mumol/l of aprotinin blocked 100% of this consumption in plasma. With increasing concentration of aprotinin in serum, a decreasing consumption of alpha 2-M and especially of alpha 1-PI was observed on the addition of trypsin. The high aprotinin concentration needed to block trypsin-induced kininogen cleavage in human serum or plasma may explain the poor clinical effect of aprotinin to date in human acute pancreatitis.

Animals↗
PubMed1983

Neurohormonal peptides in endocrine tumors of the pancreas, stomach, and upper small intestine: I. An immunohistochemical study of 27 cases.

Preliminary observations have indicated the existence of characteristic spectra of gastroenteropancreatic (GEP) neurohormonal peptides in endocrine tumors arising in foregut, midgut, and hindgut derivatives. In order to further explore this feature of GEP endocrine neoplasms, islet cell tumors from 14 patients were studied, as were endocrine tumors of the stomach, duodenum, and upper jejunum from 6, 5, and 2 patients, respectively. All tumors were examined immunohistochemically with antisera raised against islet hormones [insulin, somatostatin, glucagon, pancreatic polypeptide (PP)], peptides of the gastrin family [gastrin, cholecystokinin (CCK)], peptides of the secretin family [secretin, vasoactive intestinal peptide (VIP)], and substance P, neurotensin, leu-enkephalin, beta-endorphin, motilin, calcitonin, and ACTH. In addition, an ultrastructural investigation was made. Whenever possible, the immunohistochemical observations were correlated with the clinical manifestations and with the results of radioimmunochemical determination of GEP neurohormones in the blood. The pattern of immunoreactive neurohormonal peptides and the clinical picture were those to be expected in endocrine tumors arising in foregut derivatives. Some principles are proposed for the classification of GEP endocrine tumors on the basis of their histopathologic growth pattern, their spectrum of neurohormonal peptides, and their clinical manifestations.

Adult↗
PubMed1982

An in vitro study of the influence of plasma protease inhibitors and aprotinin on trypsin-induced C3 cleavage in human serum.

Cleavage of native C3 in human serum following the addition of increasing amounts of human cationic trypsin was studied using an in vitro model. The cleavage was correlated with the degree of saturation of the plasma protease inhibitors alpha 2-macroglobulin and alpha 1-antitrypsin, and also with varying amounts of aprotinin (Trasylol). When alpha 2-macroglobulin reached 70% saturation, there was a prompt cleavage of most of the native C3 in spite of 90% free alpha 1-antitrypsin. The consumption of alpha 2-macroglobulin, and especially of alpha 1-antitrypsin, decreased with increasing concentrations of aprotinin. Aprotinin was needed in a concentration of 60 microM to block trypsin-induced C3 cleavage almost completely. This concentration is about 20 times higher than ever used clinically. One possible explanation of the poor clinical effect of aprotinin to date in human pancreatitis is the need for this high concentration.

Aprotinin↗
PubMed1982

Demonstration of gamma-trace in normal endocrine cells of the adrenal medulla and in phaeochromocytoma. An immunohistochemical study in monkey, dog and man.

gamma-Trace was demonstrated by the immunohistochemical peroxidase/anti-peroxidase technique to occur in normal chromaffin cells of the adrenal medulla from African green monkey, capuchin monkey and beagle dog and in the cells of a norepinephrine-producing human phaeochromocytoma. The presence of gamma-trace in the endocrine epithelial cells of the adrenal medulla suggests that gamma-trace might be related to the neuroendocrine system.

Adrenal Gland Neoplasms↗
PubMed1980

Primary carcinoma of the duodenum.

Sixty-six patients with primary adenocarcinomas of the duodenum recorded by the Swedish Cancer Register during 1958-1973 are reviewed. The mean age was 66 years, and female:male ratio 1.2:1.0. The predominant symptom was duodenal obstruction. Correct diagnosis was made in 68% by conventional barium meal examination. Hypoton duodenography and duodenoscopy are necessary diagnostic aids. In 25% of the patients the diagnosis was first made at postmortem examination. Thirty-two patients had metastases at first diagnosis. Forty-three per cent were radically operated and 43% palliatively. The operative mortality after curative operations was 25% with no difference correlated to operative methods with the exception of pure polyp extirpation where no patient died. The overall one-year survival was 67% and five-year 18%. There was a tendency for longer survival time for patients with more distally situated carcinomas. Duodenopancreatectomy gave a longer survival time than duodenal resection.

Adenocarcinoma↗
PubMedDate not supplied

Femoral hernia: clinical significance of radiologic diagnosis.

UNLABELLED: A retrospective study of 18 patients with femoral hernia assessed by herniography is presented. Although a palpable lump was present in 11 patients (61%), the diagnosis of a femoral hernia was not made before herniography. Surgical exploration was performed in 12 patients and a femoral hernia was found and repaired with beneficial outcome in 9 of them. IN CONCLUSION: herniography is of value for the diagnosis of a femoral hernia in patients with obscure groin pain.

Female↗